Vitamin K2 and D3: Benefits, Dosage, Side Effects and Who Should Not Take It

Vitamin D helps you absorb calcium. Vitamin K2 switches on the proteins that put that calcium into bone. That is why people take them together.

The bone evidence is decent but not settled. The artery evidence is weaker than supplement labels suggest. And if you take warfarin, vitamin K2 is not for you without your doctor.

Vitamin K2 and D3 benefits

The trial I posted about is this one. 92 women with osteoporosis, all more than 5 years past menopause, were split into four groups: vitamin D3, vitamin K2, both, or calcium. After 2 years the calcium group had lost bone density in the spine. The D group and the K group both did better than calcium. The group taking both did better than every other group. (Iwamoto 2000)

Two details matter. The K2 was menatetrenone (MK-4) at 45 mg a day, which is a drug-level dose. And the D3 was 1-alpha-hydroxyvitamin D3, an activated form, not the plain D3 in a normal supplement.

Vitamin K2 and calcium

Osteocalcin is the protein that binds calcium into bone. It only works after vitamin K has activated it. The inactive form is called undercarboxylated osteocalcin, and it shows up in blood.

• It predicts fractures. In 195 elderly women in care homes, those with elevated undercarboxylated osteocalcin had 5.9 times the risk of hip fracture over 18 months. (Szulc 1993)
• Confirmed in a bigger group. In a study drawn from 7,598 healthy women over 75, 104 who broke a hip were compared with 255 who did not. The highest levels of the inactive form went with 1.9 times the odds of hip fracture, independent of bone density. (Vergnaud 1997)
• K2 lowers it, and fractures fell in one trial. 241 osteoporotic patients got 45 mg of K2 a day or nothing for 24 months. Clinical fractures were more frequent in the untreated group. Spine density fell 3.3% without treatment and 0.5% with K2. (Shiraki 2000)
• A low dose over 3 years. 244 healthy postmenopausal women took 180 micrograms of MK-7 or placebo. MK-7 slowed the loss of bone density at the spine and femoral neck, but not at the total hip. (Knapen 2013)

In my view calcium and vitamin K belong together. Calcium is the building material and vitamin K is what lets the bone hold on to it. I get calcium from milk and cheese.

Vitamin K2 vs K1

• Where they are. K1 is mainly in green vegetables. K2 is in meat, liver, butter, egg yolk, natto, cheese and curd cheese. (Schurgers 2000)
• How long they last. In healthy volunteers both were absorbed well and peaked at 4 hours. MK-7 has a very long half-life, so with daily use it built up to levels 7 to 8 times higher, and it activated osteocalcin more completely than K1. (Schurgers 2007)
• The heart data. In 4,807 people in the Rotterdam Study, the highest third of K2 intake had a relative risk of 0.43 for death from coronary heart disease and less severe aortic calcification. K1 intake was not related to any outcome. This is an observational study. (Geleijnse 2004)

Vitamin K2 foods

From the food database above: natto, cheese and curd cheese, egg yolk, butter, liver and meat. Natto is in a class of its own. In that study, blood levels of K2 after eating natto were about 10 times higher than the K1 levels after eating spinach.

Vitamin K2 dosage for adults

I am not going to give you a dose. These are the doses used in the trials:

• MK-4: 45 mg a day, in the Japanese osteoporosis trials. That is a drug-level dose.
• MK-7: 180 micrograms a day for 3 years in the bone trial, and 720 micrograms a day for 2 years in the heart valve trial below.

Notice that MK-4 is dosed in milligrams and MK-7 in micrograms. They are not interchangeable. I take K2 with vitamin E and calcium, and I do not take the K and the E at the same time of day. That spacing is my habit, not a study result.

Vitamin K2 side effects and warfarin

This is the part that can hurt someone.

Warfarin and related blood thinners work by blocking vitamin K. Taking vitamin K works against the drug. In 18 healthy volunteers put on the anticoagulant acenocoumarol, 45 micrograms of MK-7 a day lowered the INR by about 40%. Even 10 micrograms was judged to cause a clinically relevant drop in at least 40% of them. The authors concluded that MK-7 supplements need to be avoided by patients on this kind of drug. (Theuwissen 2013)

Ten micrograms is less than most K2 capsules contain. If you take warfarin or another vitamin K antagonist, do not start, stop or change vitamin K2 without the doctor who manages your INR.

For everyone else the record is mostly quiet. A meta-analysis of 14 trials and 1,533 patients found no significant difference in adverse events between vitamin K and control. (Li 2023) At the 45 mg MK-4 dose, another meta-analysis found more adverse events and adverse drug reactions than placebo, though not more serious ones. (Su 2019)

The honest part

• Fractures are not proven. An updated meta-analysis of 36 trials found lower odds of clinical fractures with vitamin K, 0.72, but the result lost significance when only the better-quality trials were counted. There was no difference in vertebral fractures. The authors wrote that the integrity of some of the earlier evidence has been questioned. (Mott 2019)
• In the 241-patient trial, the K2 group had fewer fractures but did not gain bone density. It only lost less.
• Arteries did not respond in the best trial. 365 men with a calcified aortic valve took 720 micrograms of MK-7 with 25 micrograms of vitamin D, or placebo, for 2 years. The calcium score rose by 275 units on the vitamins and 292 on placebo, no real difference. The blood marker of vitamin K status improved, the calcification did not. (Diederichsen 2022)
• The pooled analysis of 14 trials did find slower progression of coronary calcium, and its authors asked for better trials before anyone relies on it.
• The Rotterdam result is an association. People who eat more cheese and meat differ in many ways.

So K2 with D3 is reasonable for bones if you are not on a blood thinner. It is not a proven way to clean arteries. My view on vitamin D: get sun first, and test your blood level before you take high doses.

What Ray Peat wrote about these vitamins is in Ray Peat on vitamins A, D and K. My long read on calcium is the calcium paradox.

Quick answers

What are the benefits of vitamin K2 and D3 together?

In a 2-year trial of 92 postmenopausal women with osteoporosis, the group taking vitamin K2 with vitamin D3 gained more spine bone density than the groups taking either alone or calcium. The doses were prescription-level.

What does vitamin K2 do with calcium?

Vitamin K activates osteocalcin, the protein that binds calcium into bone. High blood levels of the inactive form of osteocalcin predicted hip fractures in elderly women in two studies.

What are the side effects of vitamin K2?

Trials report few. The main danger is the interaction with warfarin and similar anticoagulants: as little as 10 micrograms of MK-7 a day reduced anticoagulation in some volunteers. At 45 mg a day of MK-4, adverse events were more common than on placebo.

What is the vitamin K2 dosage for adults?

There is no single established dose. Trials used 180 micrograms a day of MK-7 for bone, 720 micrograms a day in a heart valve trial, and 45 mg a day of MK-4 in Japanese osteoporosis trials.

What foods contain vitamin K2?

Natto, cheese and curd cheese, egg yolk, butter, liver and meat. Vitamin K1 is found mainly in green vegetables.

What is the difference between vitamin K2 and K1?

K1 comes mainly from green vegetables and K2 from animal and fermented foods. MK-7, a form of K2, has a much longer half-life, builds up to 7 to 8 times higher blood levels with daily use, and activated osteocalcin more completely in a comparison study.